This is a competitive renewal application where we propose to study cortical network differences between neuropathic and inflammatory chronic pain conditions, and determine the re-organizational properties of these networks as a function of time and of therapy. In the last funding cycle we developed noninvasive brain imaging techniques tailored specifically to study clinical pain conditions. With these tools we studied two populations of chronic neuropathic pain conditions, and showed that the brain network underlying chronic pain is distinct from that of acute pain, that it may be reorganizing in time and also undergoing a neurodegenerative process. In this cycle 3 groups of chronic pain patients are studied, compared and contrasted to matched normal volunteers: chronic inflammatory or neuropathic back pain (CLBP), chronic post herpetic neuropathy (PHN), and chronic osteoarthritic knee joint pain (OAP). [unreadable] [unreadable] In Aim 1 we determine the cortical network underlying ongoing, spontaneously fluctuating, pain perception in chronic neuropathic and inflammatory conditions, by comparing fMRI results between CLBP, PHN, & OAP. In Aim 2 we determine the cortical network underlying stimulus-evoked chronic neuropathic and inflammatory conditions, by comparing fMRI results for tactile allodynia in PHN to joint stimulation-evoked pain in OAP. In Aim 3 we attempt to find a causal link between brain gray and white matter density decreases and gray and white matter chemical decreases, mainly of N-acetylaspartate (NAA), as a result of chronic pain, differentiating between neuropathic and inflammatory conditions. These entail MRI-based morphometric studies, MRI spectroscopic measures of brain gray matter and white matter chemistry, and water diffusion based studies of white matter tracks. These studies are done in a cross-sectional and longitudinal design. In Aim 4 we study the reversibility of cognitive deficits, chemical concentration decreases and gray matter density decreases in OAP and PHN patients before and after pain therapy. [unreadable] [unreadable]